Dr. Brian L. Edlow is a Neurocritical Care Neurologist at Massachusetts General Hospital (MGH) whose goal is to become an independent investigator with expertise in the neuroimaging and neuropathology of traumatic brain injury. His career development plan leverages the resources of a world-class environment by bringing together a multidisciplinary team of mentors and collaborators centered at a leading academic institution in Boston, MGH. Dr. Edlow has already obtained preliminary results demonstrating the feasibility of a research plan that uses an advanced magnetic resonance imaging technique, high angular resolution diffusion imaging (HARDI), to map the structural connectivity, or connectomics, of the brainstem arousal network in patients with traumatic coma. Under the mentorship of primary mentor Dr. Bruce Fischl, and co-mentors Drs. Hannah Kinney, Joseph Giacino, Emery Brown, and Jonathan Rosand, Dr. Edlow proposes: 1) To validate structural connectomic maps of the brainstem arousal network by correlating ex vivo HARDI tractography with histopathology in brain specimens from civilians and military personnel who die after traumatic coma; 2) to determine the association between ex vivo structural connectomic maps of the brainstem arousal network and the highest level of consciousness attained in civilians and military personnel who die during recovery from traumatic coma; and 3) to determine the prognostic utility of in vivo structural connectomic maps of the brainstem arousal network for predicting recovery of consciousness in patients with acute traumatic coma. The overall goal of this project is to elucidate the neuroanatomic basis for recovery of consciousness in patients with traumatic coma and to create a prognostic model that provides families with more accurate, personalized information about their loved ones' chances of recovery. By bringing together cutting edge neuroimaging technology at MGH and a team of mentors with relevant expertise, this project will generate new insights into the neuroanatomy of consciousness and will create new opportunities for treatments of acute traumatic coma. In the long term, Dr. Edlow's career goal is to develop novel therapies aimed at promoting recovery of consciousness in patients with traumatic coma by replacing, bypassing, or augmenting injured connections within the brainstem arousal network. The proposed patient-oriented research project, in concert with mentorship and a structured didactic curriculum in neuroimaging, neuropathology, network statistics, neurobehavioral assessment of disorders of consciousness, and clinical management of traumatic brain injury, will provide Dr. Edlow with the skills that are essential for him to develop an independent career in traumatic brain injury research at the cutting edge of science.